Dr Burke on Treatment Paradigm Shifts in Relapsed DLBCL

John Burke, MD, hematologist, medical oncologist, blood cancer specialist, Rocky Mountain Cancer Centers, discusses the evolution of the diffuse large B-cell lymphoma (DLBCL) treatment paradigm.

One major evolution in the DLBCL therapeutic landscape has been the advent of CAR T-cell therapy, Burke says. The phase 3 ZUMA-7 trial (NCT03391466) showed that the CAR T-cell therapy axicabtagene ciloleucel (axi-cel; Yescarta) elicited superior event-free survival (EFS) outcomes vs standard-of-care (SOC) chemoimmunotherapy, high-dose chemotherapy, and autologous stem cell transplant in patients with DLBCL whose disease relapsed within 1 year of initiating their first line of chemoimmunotherapy. At a median follow-up of 24.9 months, the median EFS was 8.3 months (95% CI, 4.5-15.8) in the axi-cel arm vs 2.0 months (95% CI, 1.6-2.8) in the SOC arm, with respective 24-month EFS rates of 41% (95% CI, 33%-48%) and 16% (95% CI, 11%-22%), respectively (HR, 0.40; 95% CI, 0.31-0.51; P < .001).

Another advance in the DLBCL armamentarium is the increased use of regimens that use novel targeted agents, such as polatuzumab vedotin-piiq (Polivy) plus chemotherapy, tafasitamab-cxix (Monjuvi) plus lenalidomide (Revlimid), and loncastuximab tesirine-lpyl (Zynlonta) in patients with relapsed disease, Burke explains. Overall, several types of therapies have broadened the DLBCL treatment paradigm, Burke notes.

In the frontline DLBCL setting, the phase 3 POLARIX trial (NCT03274492) showed a progression-free survival (PFS) benefit with polatuzumab vedotin in combination with R-CHP (rituximab [Rituxan], cyclophosphamide, doxorubicin, and prednisone; pola-R-CHP) vs SOC R-CHOP (cyclophosphamide, doxorubicin, prednisone, rituximab, and vincristine). At a median follow-up of 28.2 months, the PFS rate was 76.7% (95% CI, 72.7%-80.8%) in the pola-R-CHP arm vs 70.2% (95% CI, 65.8%-74.6%) in the R-CHOP arm. The findings from this trial supported the April 2023 FDA approval of pola-R-CHP in patients with previously untreated DLBCL.

Evolutions in the treatment of patients with DLBCL are occurring in the frontline, early relapse, and salvage therapy settings, Burke emphasizes. In addition, an increasing number of novel agents are supplanting chemoimmunotherapy as the SOCs in heavily pretreated patients, Burke concludes.